Insecticide malathion

The development of malathion in 1950 was an important milestone in the emergence of selective insecticides. Malathion is from one-half to one-twentieth as toxic to insects as parathion but is only about one two-hundredths as toxic to mammals. Its worldwide usage in quantities of thousands of metric tons in the home, garden, field, orchard, woodland, on animals, and in pubHc health programs has demonstrated substantial safety coupled with pest control effectiveness. The biochemical basis for the selectivity of malathion is its rapid detoxication in the mammalian Hver, but not in the insect, through the attack of carboxyesterase enzymes on the aUphatic ester moieties of the molecule. 

Self-Test 8.12B Use the data in Table 8.8 to determine at what temperature a 0.050 mol-kg 1 solution of the insecticide malathion, C10H19O6PS2, in camphor will freeze. 

The insecticide malathion was the hero in the 1976 tragedy in Pakistan. Poisoning started after measures were taken to fight malaria. At least 2800 of the 7500 workers in this area were poisoned [37]. When studied, the more highly toxic iso-malathion was found together with malathion in their bodies. It is known that iso-malathion transforms into the more highly toxic malaoxon, both in storage and directly in the environment. 

Currently there are few insecticides registered as surface treatments to control stored-product insects. For years the organophosphate insecticide malathion was used as a surface treatment for structural facilities, but stored-product insects throughout the world have developed extensive resistance to malathion (Subramanyam and Hagstrum, 1996). Most of the resistance reports were generated from studies with bulk grains, but in the United States, resistance has been documented for field populations of the red flour beetle, T. castaneum (Herbst), and the confused flour beetle, T. confusum (DuVal), collected from flour mills (Arthur and Zettler, 1991, 1992 Zettler, 1991). Populations of the Indianmeal moth, the almond moth, and the red flour beetle collected from bulk peanuts and empty warehouses were also highly resistant to malathion (Arthur et al., 1988 Halliday et al., 1988). 

Microorganisms can inactive toxicants by cleavage of a bond by the addition of water. Such reactions may involve a simple hydrolysis of an ester bond, as with the insecticide Malathion by a carboxyesterase enzyme ... 

Selective bioactivation (toxification) is illustrated in the case of the insecticide malathion (3.35). This acetylcholinesterase inhibitor is desulfurized selectively to the toxic malaoxon, but only by insect and not mammalian enzymes. Malathion is therefore relatively nontoxic to mammals (LDjg = 1500 mg/kg, rat p.o.). Higher organisms rapidly detoxify malathion by hydrolyzing one of its ester groups to the inactive acid, a process not readily available to insects. This makes the compound doubly toxic to insects since they cannot eliminate the active metabolite. 

Different species have developed different pathways and this can have a significant impact on their use. Consider the metabolism of the insecticide malathion. 

Dispositional interactions are those in which one chemical affects the disposition of the other, usually metabolism. Thus, one chemical may increase or inhibit the metabolism of another to change its toxicity. For example, 2,3-methylenedioxynaphthalene inhibits cytochrome P-450 and so markedly increases the toxicity of the insecticide carbaryl to flies (potentiation) (see chap. 5). Another example, which results in synergy, is the increased toxicity of the organophosphorus insecticide malathion (see chap. 5) when in combination with another organophosphorus insecticide, EPN. EPN blocks the detoxication of malathion. Many chemicals are either enzyme inhibitors or inducers and so can increase or decrease the toxicity of other chemicals either by synergism or potentiation (see chap. 5). 

Hydrolytic reactions. There are numerous different esterases responsible for the hydrolysis of esters and amides, and they occur in most species. However, the activity may vary considerably between species. For example, the insecticide malathion owes its selective toxicity to this difference. In mammals, the major route of metabolism is hydrolysis to the dicarboxylic acid, whereas in insects it is oxidation to malaoxon (Fig. 5.12). Malaoxon is a very potent cholinesterase inhibitor, and its insecticidal action is probably due to this property. The hydrolysis product has a low mammalian toxicity (see chap. 7). 

One of the classic cases is the potentiation of the insecticide malathion by another insecticide, EPN, the LD50 of the mixture being dramatically lower than that of either compound alone. This potentiation can also be seen between malathion and certain contaminants that are formed during synthesis, such as isomalathion. For this reason quality control during manufacture is essential. This example of potentiation involves inhibition, by EPN or isomalathion, of the carboxylesterase responsible for the detoxication of malathion in mammals. 

Table II shows pesticides used by the US Forest Service and the amounts used in 1980. On this list 2,4-D is in first place, being used at in an amount of 215,000 pounds per year. In 1980 the second most commonly used pesticide by the USFS was the insecticide malathion at in an amount of 102,000 pounds. There are only three insecticides on this list of the nine most commonly used pesticides in the USFS. The insecticide use rate will vary considerably from year to year as its use is dependent on insect outbreaks, whereas herbicides are used at a more constant rate because the appearance of weeds and brush, as they affect forest management, do not occur as periodic outbreaks.

Nishi, K., Y. Imajuku, M. Nakata, et al. 2003. Preparation and characterization of monoclonal and recombinant antibodies specific to the insecticide malathion. J. Pestic. Sci. 28 301-309. 

In the 1970s, organophosphorus compounds became the leading type of insecticide. Over 40 such compounds have been registered in the United States as insecticides. The first organophosphorus insecticide was synthesized in 1938 and is known as tetraethyl pyrophosphate (TEPP). Another phosphate insecticide, Malathion is synthesized by condensing diethyl maleate with the o,o-dimethyl phosphorodithioic acid. 

Spiher, D. (1961) A digest of available information on insecticide malathion. Adv. Pest. Control Res. 4, 249. 

Of great interest is contact insecticide malathion (carbophos) ... 

Although examples are known in which synergistic interactions take place at the receptor site, the majority of such interactions appear to involve the inhibition of xenobiotic-metabolizing enzymes. Two examples involve the insecticide synergists, particularly the methylenedioxyphenyl synergists, and the potentiation of the insecticide malathion by a large number of other organophosphate compounds. 

The well-known selectivities of some organophosphates may be explained by the balance of enzymatic events. The reduced toxicity of the insecticide malathion to mammals is largely the result of rapid activation by desulfuration in the insect and the more rapid detoxificaton by carboxylesterases and glutathione transferases in the mammal (3). Design of new pest bioregulators should exploit enhanced activation and decreased detoxification capabilities in the targeted pests. 

To increase the marketability of Collego, its compatibility with chemical pesticides has been investigated. Mixtures of CGA with propanil [N-(3,4-dichlorophenyl)propanamide], molinate [S-ethyl hexahydro-lH-azepine-l-carbothioate], 2,4,5-T, and benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate] were detrimental to CGA s efficacy (31). If, however, propanil, 2,4,5-T, fentin hydroxide (triphenyltin hydroxide), pencycuron N-[(4-chlorophenyl)methyl]-N-cyclopentyl-N -phenylurea), each at 0.56 kg ai/ha, and SN-84364 [3 -isopropoxy-2-(trifluoromethyl) benzanilide] (at 0.40 kg ai/ha) were applied after CGA treatment, disease and development were not inhibited (32). The herbicides, acifluorfen 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid) (0.56 kg ai/ha) and bentazon [3-(1-methylethyl)-(IH)-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide] (0.56 to 1.1 kg ai/ha), or the insecticides, malathion [diethyl(dimethoxyphosphinothioylthio)succinate] (0.56 kg ai/ha) and carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate), (0.56 kg ai/ha) could be applied with CGA from a single tank mixture (33-34). ... 

It binds to the enzyme and destroy the active site, or otherwise screw the protein. Suicide inhibitors, a special class of such inhibitors, are activated by the normal catalytic activity of the enzyme, but form an intermediate that binds to and destroys the active site. Irreversible inhibitors bind tightly (often covalently) to the enzyme and cannot be removed by dialysis. They include such things as nerve gases (Sarin, DIPF, Tabun) and insecticides (Malathion). 

Addition of an acid dithiophosphoric acid-0,0-diester to a -C=C- or C=0 double bond results in a neutral 0,0,S-triester as, for example in the synthesis of the insecticide Malathion ... 

Sulfur sometimes plays a role as propesticide in compounds in which biological activity is enhanced by enzymic oxidation thus, for the insecticide malathion (5) (Figure 2), potency is increased by the in vivo conversion of the thiophosphoryl P=S into the phosphoryl P=0 group in the insect. 

The most important inhibitors of CarbEs are organo-phosphorus insecticides (malathion, parathion, para-oxon, methyl parathion, EPN, and others), nerve agents (DFP, soman, sarin, tabun, and VX) and carbamate insecticides (carbofuran, carbaryl, aldicarb, propoxur, oxamyl, methomyl, and others). Organo-phosphorus toxicants inhibit CarbEs irreversibly by phosphorylation and carbamates inhibit CarbEs reversibly by carbamylation similar to the basic mechanism (i.e., acylation of the active site) ... 

Examples of organophosphates include the insecticides malathion, parathion, diazinon, fenthion, azinphos methyl, terbufos, dichlorvos, and chlorpyr-ifos the nerve gases soman, sarin, tabun, and VX the ophthalmic agent echothiophate the anthelmintic trichlorfon tricresyl phosphate-containing... 

Explain why the insecticide malathion (Figure 5.9) is toxic to insects but relatively non-toxic to humans. 

A sample of the insecticide malathion (VX simulant) was obtained by diluting 4 mL of Dexol in 1 L of distilled water. The spectra of its fluorescence, excited by 266 mn and 355 nm ultra-violet lasers, are shown in Figs. 8-9. As can be seen, there appears to be a distinct fluorescence emission near 360 mn. Further work is being conducted to better quantify our results. 

Organoposphates Lipid-soluble, long-acting irreversible inhibitors Rx—glaucoma (echothiophate) Note use as insecticides (malathion, parathion) and as nerve gas (sarin)... 

Fortunately, however, certain types of bacteria manufacture an enzyme called phospho-triesterase (PTE) that inactivates sarin and other organophosphate molecules like it, some of which are found in certain insecticides but are hundreds of times less toxic to people. Certain organophosphates, such as the common insecticide malathion, kill insects because, unlike animals, bugs lack an enzyme that breaks down this chemical. For many years Frank Raushel of Texas A M University in College Station has studied the PTE enzyme, and recently he and his colleague Hazel Holden of the University of Wisconsin-Madison cleared a substantial hurdle They identified the three-dimensional structure— a molecular snapshot —of what this enzyme looks like. This information will help scientists understand how the enzyme works—and could reveal how to engineer one that works even better. 

Metabolism of the local anaesthetic procaine provides an example of esterase action, as shown in figure 4.42. This hydrolysis may be carried out by both a plasma esterase and a microsomal enzyme. The insecticide malathion is metabolized by a carboxyl esterase in mammals, rather than undergoing oxidative desulphuration as in insects (figure 5,10). 

Carbon disulfide interacts with several organophosphorus compounds including the insecticides malathion and parathion. Metabolism of malathion and parathion requires cytochrome P-450 and is thus inhibited by carbon disulfide (Dalvi and Howell 1978). It is important to note that carbon disulfide would potentiate the toxic effect of compounds that require cytochrome P-450 microsomal metabolism for detoxification. 

Figure 23. Phosphorothionate and phosphorodithioate ester insecticides. Malathion contains hydrolyzable carboxyester linkages (Monahan,2000).

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